The heart consists of several functionally different cell groups such as impulse generating nodal tissue, impulse conducting fiber and mechanically contracting ventricular muscle. The electrophysiological effects of digitalis in the nodal tissue are different from those in the ventricle. Intracellular Na ion content of nodal tissue is 4 to 5 times higher than that in the ventricle so that the intracellular and extracellular Na ion gradient in the nodal tissue is very little. This suggests the operational status of active Na ion pumping mechanism in the nodal tissue is probably different from that in the ventricle. Digitalis is also a specific inhibitor of Transport ATPase (Na ion, K ion-ATPase). Its inhibition by digitalis may be related with the production of positive inotropic action and/or toxic effects of digitalis. Therefore, the aims of this proposed research is 1) to determine Na ion, K ion-ATPase activity in the nodal tissue; and 2) to determine the effect of digitalis on Na ion, K ion-ATPase activity and the content of Na ion and K ion in the nodal tissue. My broad research objective is to define the molecular mechanism of digitalis induced arrhythmias and antiarrhythmic agents. Three groups of intact open-chest dogs will be used. The control group will be sham-operated and will not receive any therapy. The second group will receive a dose of digitalis that is known to produce persistent arrhythmias. The last group will be treated with a typical antiarrhythmic drug after induction of arrhythmias, as in the second group. Samples of various functional tissues will be excised and assayed for Na ion, K ion-ATPase by a new fluorimetric method and the contents of Na ion and K ion by a conventional flamephotometer. This study should reveal, if there is as claimed in the ventricle, a relationship between Na ion, K ion-ATPase activity in functionally distinctly different cardiac tissues and the toxic arrhythmogenic action of digitalis. An understanding of the molecular mechanism of action of the digitalis toxicity should provide a basis for rational therapy of this group of compounds.